Hepatitis C virus (HCV) infection becomes persistent in the majority of instances in the face of a humoral and cellular immune response, and persistent HCV infection is associated with chronic hepatitis. In particular, cytotoxic T lymphocytes (CTL), crucial in the eradication of virus-infected cells, have been observed in the liver and the peripheral blood of chronically infected patients, suggesting that CTL cannot completely eliminate the virus, and may contribute to chronic liver injury. In this review, the potential host and the viral factors involved in the pathogenesis of chronic HCV infection will be discussed with emphasis on the HLA-A2 restricted peripheral blood CTL response and its relationship to liver disease and viral load.